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Global Translational Medicine Evidence-based approach for TCM development

potentially limiting the diversity and availability of TCM Table 2. Composite hypotheses for clinical evaluation of
products in the Western market. both safety and efficacy 15
Despite the efforts to integrate TCM into the Western Efficacy/safety S N E
healthcare system through regulatory frameworks, the S SS SN SE
fundamental differences between WM and TCM, as N NS NN NE
discussed in the previous section, present challenges in
directly applying Western pharmaceutical development E ES EN EE
processes to TCM. This has led to the recognition that Abbreviations: E: Equivalence; N: Non-inferiority; S: Superiority.
a more tailored approach, which considers the unique
characteristics of TCM, is necessary for its successful Similarly, for safety assessment, investigators analyze the
modernization and development. safety profile of the treatment, including adverse events
and other relevant parameters, to determine whether the
4. Modernization of TCM development test treatment is superior, non-inferior, or equivalent to
the control in terms of safety. By incorporating both safety
Given the limitations of applying traditional Western
pharmaceutical development processes to TCM, an and efficacy considerations into composite hypotheses,
alternative approach is to consider the modernization of researchers can develop a more comprehensive approach
to evaluating TCM treatments, acknowledging the unique
TCM development. This approach aims to be a scientifically
objective, evidence-based method that respects the unique characteristics of TCM while ensuring that the treatments
characteristics of TCM while ensuring the safety and meet modern standards for safety and effectiveness.
efficacy of TCM products. In the modernization of TCM It should be noted that achieving statistical significance
development, several key aspects must be considered from with the desired power for correctly detecting clinically
both clinical and regulatory perspectives: meaningful differences in both safety and efficacy
parameters (endpoints) in clinical trials will require a
4.1. Clinical investigation much larger sample size. To overcome this problem, some
In the development of WMs, the traditional Western out-of-the-box innovative thinking is necessary, which will
approach is to power the study based on the efficacy be further discussed in a later section of this article.
endpoint alone. The WM will be approved if the null
hypothesis of ineffectiveness is rejected and there appears 4.2. Establishment of standards for TCM
to be no evidence of safety concerns. This approach has As the traditional subjective experience-based assessment,
been criticized because the clinical study is powered based regardless of the sufficient documentation, is not convincing
on the efficacy endpoint alone, which targets specific and hence not acceptable for providing substantial
organs but does not account for safety concerns that evidence in support of regulatory submissions of TCMs,
may be induced by other organs. As a result, many drug the modernization of TCM development requires a set
products were withdrawn due to safety concerns after of standards for diagnostic procedures, evaluation, and
regulatory approval. A typical example is the withdrawal regulatory review for an accurate and reliable assessment
of Vioxx (intended for pain relief), which was approved by of the safety and efficacy of TCM under development
the FDA in 1999 but was withdrawn in 2004 due to a high scientifically. The standards for diagnostic procedures,
risk of heart attack and stroke. 14 evaluation, and regulatory review can help in providing
TCM takes a holistic approach to healthcare, aiming objective and substantial evidence for the evaluation of the
to restore and maintain the overall balance and harmony safety and efficacy of the TCMs under investigation. Unlike
of the body’s systems, in contrast to WM, which typically WMs, currently, there are no universally accepted objective
focuses on targeting specific organs or systems affected standards for diagnostic and evaluation procedures for
by a disease. Given these philosophical differences, TCMs across different therapeutic areas. 16
modernizing the development of TCM should involve 4.3. Validation against western standards
testing composite hypotheses that consider both safety and
efficacy in clinical investigations, as proposed by Chow and Since there are no universally accepted objective
Shao (Table 2). When assessing the efficacy of a treatment, diagnostic and evaluation procedures for TCMs, the
15
researchers commonly employ tests for superiority (S), development and validation of tools such as quality-of-
non-inferiority (N), or therapeutic equivalence (E) life-like instruments is necessary. For the validation of the
hypotheses, which compare the performance of the new developed instruments, it is suggested that the validation
treatment to an existing control or standard of care. be performed against well-established Western standards

Volume 3 Issue 3 (2024) 4 doi: 10.36922/gtm.4190